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1.
Health Technol Assess ; 16(44): 1-469, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23158845

RESUMO

BACKGROUND: There is now a considerable body of evidence revealing that a number of ethnic minority groups in the UK and other economically developed countries experience disproportionate levels of morbidity and mortality compared with the majority white European-origin population. Across these countries, health-promoting approaches are increasingly viewed as the long-term strategies most likely to prove clinically effective and cost-effective for preventing disease and improving health outcomes in those with established disease. OBJECTIVES: To identify, appraise and interpret research on the approaches employed to maximise the cross-cultural appropriateness and effectiveness of health promotion interventions for smoking cessation, increasing physical activity and improving healthy eating for African-, Chinese- and South Asian-origin populations. DATA SOURCES: Two national conferences; seven databases of UK guidelines and international systematic reviews of health promotion interventions aimed at the general population, including the Clinical Evidence, National Institute for Health and Clinical Excellence and Scottish Intercollegiate Guidelines Network databases (1950-2009); 11 databases of research on adapted health promotion interventions for ethnic minority populations, including BIOSIS, EMBASE and MEDLINE (1950-2009); and in-depth qualitative interviews with a purposive sample of researchers and health promoters. REVIEW METHODS: Theoretically based, mixed-methods, phased programme of research that involved user engagement, systematic reviews and qualitative interviews, which were integrated through a realist synthesis. Following a launch conference, two reviewers independently identified and extracted data from guidelines and systematic reviews on the effectiveness of interventions for the general population and any guidance offered in relation to how to interpret this evidence for ethnic minority populations. Data were thematically analysed. Reviewers then independently identified and critically appraised studies of adapted interventions and summarised data to assess feasibility, acceptability, equity, clinical effectiveness and cost-effectiveness. Interviews were transcribed, coded and thematically analysed. The quantitative and qualitative data were then synthesised using a realist framework to understand better how adapted interventions work and to assess implementation considerations and prioritise future research. Our preliminary findings were refined through discussion and debate at an end-of-study national user engagement conference. RESULTS: Initial user engagement emphasised the importance of extending this work beyond individual-centred behavioural interventions to also include examination of community- and ecological-level interventions; however, individual-centred behavioural approaches dominated the 15 relevant guidelines and 111 systematic reviews we identified. The most consistent evidence of effectiveness was for pharmacological interventions for smoking cessation. This body of work, however, provided scant evidence on the effectiveness of these interventions for ethnic minority groups. We identified 173 reports of adapted health promotion interventions, the majority of which focused on US-based African Americans. This body of evidence was used to develop a 46-item Typology of Adaptation and a Programme Theory of Adapted Health Promotion Interventions. Only nine empirical studies directly compared the effectiveness of culturally adapted interventions with standard health promotion interventions, these failing to yield any consistent evidence; no studies reported on cost-effectiveness. The 26 qualitative interviews highlighted the need to extend thinking on ethnicity from conventional dimensions to more contextual considerations. The realist synthesis enabled the production of a decision-making tool (RESET) to support future research. LIMITATIONS: The lack of robust evidence of effectiveness for physical activity and healthy-eating interventions in the general population identified at the outset limited the comparative synthesis work we could undertake in the latter phases. Furthermore, the majority of studies undertaking an adapted intervention were conducted within African American populations; this raises important questions about the generalisability of findings to, for example, a UK context and other ethnic minority groups. Lastly, given our focus on three health areas and three populations, we have inevitably excluded many studies of adapted interventions for other health topics and other ethnic minority populations. CONCLUSIONS: There is currently a lack of evidence on how best to deliver smoking cessation, physical activity and healthy eating-related health promotion interventions to ethnic minority populations. Although culturally adapting interventions can increase salience, acceptability and uptake, there is as yet insufficient evidence on the clinical effectiveness or cost-effectiveness of these adapted approaches. More head-to-head comparisons of adapted compared with standard interventions are warranted. The Typology of Adaptation, Programme Theory of Adapted Health Promotion Interventions and RESET tool should help researchers to develop more considered approaches to adapting interventions than has hitherto been the case. FUNDING: The National Institute for Health Research Health Technology Assessment programme.


Assuntos
Povo Asiático , População Negra , Características Culturais , Dieta , Promoção da Saúde/métodos , Atividade Motora , Abandono do Hábito de Fumar/etnologia , Medicina Baseada em Evidências , Humanos , Entrevistas como Assunto , Guias de Prática Clínica como Assunto
2.
Eur J Obstet Gynecol Reprod Biol ; 151(1): 33-7, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20456855

RESUMO

OBJECTIVE: To investigate the views of women in relation to the provision of antenatal care. METHODS: A discrete choice experiment using a sample of 100 women who were nulliparous (pregnant for the first time) and attending for routine ultrasound scan in the 20th week of their pregnancy. RESULTS: Women preferred antenatal care visits to be provided by a community midwife at a local clinic and to have 10 visits rather than 7. In addition they favoured the provision of education/preparation for birth, the use of uterine artery Doppler screening, and the provision of a telephone advice line. The results show that women were prepared to trade-off fewer antenatal care visits to ensure access to their packages of antenatal care that reflected their preferences. CONCLUSIONS: Whilst the number of antenatal care visits is important to women they may accept fewer visits if antenatal care is provided by midwives and they receive enhanced service provision such as a telephone advice line and uterine artery Doppler screening.


Assuntos
Satisfação do Paciente , Cuidado Pré-Natal/métodos , Comportamento de Escolha , Feminino , Linhas Diretas , Humanos , Tocologia , Paridade , Gravidez , Cuidado Pré-Natal/economia , Cuidado Pré-Natal/normas , Ultrassonografia , Reino Unido , Artéria Uterina/diagnóstico por imagem
3.
Health Technol Assess ; 13(53): 1-124, iii-iv, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19906334

RESUMO

OBJECTIVES: To determine the acceptability, efficacy and costs of medical termination of pregnancy (MTOP) compared with surgical termination of pregnancy (STOP) at less than 14 weeks' gestation, and to understand women's decision-making processes and experiences when accessing the termination service. DESIGN: A partially randomised preference trial and economic evaluation with follow-up at 2 weeks and 3 months. SETTING: The Royal Victoria Infirmary, Newcastle upon Tyne, UK. PARTICIPANTS: Women accepted for termination of pregnancy (TOP) under the relevant Acts of Parliament with pregnancies < 14 weeks' gestation on the day of abortion. A further group of women attending contraception and sexual health clinics participated in a discrete choice experiment (DCE). INTERVENTIONS: STOP: all women > or = 6 weeks' and < 14 weeks' gestation were primed with misoprostol 400 micrograms 2 hours before the procedure. STOP was performed under general anaesthesia using vacuum aspiration. MTOP: all women < 14 weeks' gestation were given mifepristone 200 milligrams orally, returning 36-48 hours later for misoprostol. OUTCOME MEASURES: Main outcome measure was acceptability of TOP method. Secondary outcome measures included strength of preference by willingness to pay (WTP); distress, using the Impact of Event Scale (IES); anxiety and depression; satisfaction with care; experience of care; frequency and extent of symptoms including self-assessment of pain; clinical effectiveness; and complications. A DCE was used to identify attributes that shape women's preferences for abortion services. RESULTS: The trial recruited 1877 women, 349 in the randomised arms and 1528 in the preference arms. Of those in the preference arms, 54% chose MTOP. At 2 weeks after the procedure more women having STOP would choose the same method again in the future. Acceptability of MTOP declined with increasing gestational age. The difference in acceptability between STOP and MTOP persisted at 3 months. At 2 weeks after TOP, women in the preference arms were prepared to pay more to have their preferred option. There was no difference in anxiety or depression scores in women having MTOP or STOP. However, women randomised to MTOP had higher scores on subscales of the IES at both 2 weeks and 3 months. There was no difference in IES scores between MTOP and STOP in the preference arm. Women were more likely to be satisfied overall and with technical and interpersonal aspects of care if they had STOP rather than MTOP. Experience of care scores were lower after MTOP in both randomised and preference arms. During admission women undergoing MTOP had more symptoms and reported higher mean pain scores, and after discharge reported more nausea and diarrhoea. There were no differences in time taken to return to work between groups; around 90% had returned to work and normal activity by 2 weeks. Rates of unplanned or emergency admissions were higher after MTOP than after STOP. Overall complication rates were also higher after MTOP, although this only achieved statistical significance in the preference arm. Overall, STOP cost more than MTOP due to higher inpatient standard costs. Even though complication rates were higher with MTOP, it was still more cost-effective. DCE identified three attributes with an almost equal impact on women's preferences: provision of counselling, number of days delay to the procedure, and possibility of an overnight stay. CONCLUSIONS: MTOP was associated with more negative experiences of care and lower acceptability. Acceptability of MTOP declined with increasing gestational age. MTOP was less costly but also less effective than STOP. The majority of women choosing MTOP were satisfied with their care and found the procedure acceptable. RECOMMENDATIONS FOR FURTHER RESEARCH: An audit of provision of MTOP and STOP in England and Wales is urgently required. Further studies exploring the barriers to offering women the choice of method of TOP are needed, together with research on the acceptability and effectiveness of (1) MTOP and manual VA in pregnancies below 9 weeks' gestation and (2) MTOP and dilatation and evacuation after 14 weeks' gestation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN07823656.


Assuntos
Aborto Induzido/métodos , Preferência do Paciente , Primeiro Trimestre da Gravidez , Abortivos Esteroides/administração & dosagem , Abortivos Esteroides/farmacologia , Adolescente , Adulto , Inglaterra , Feminino , Humanos , Mifepristona/administração & dosagem , Mifepristona/farmacologia , Gravidez , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
4.
Health Technol Assess ; 12(35): iii, ix-x, 1-146, 169-515, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19032882

RESUMO

OBJECTIVES: To determine the clinical effectiveness and cost utility of procedures alternative to TURP (transurethral resection of the prostate) for benign prostatic enlargement (BPE) unresponsive to expectant, non-surgical treatments. DATA SOURCES: Electronic searches of 13 databases to identify relevant randomised controlled trials (RCTs). REVIEW METHODS: Two reviewers independently assessed study quality and extracted data. The International Prostate Symptom Score/American Urological Association (IPSS/AUA) symptom score was the primary outcome; others included quality of life, peak urine flow rate and adverse effects. Cost-effectiveness was assessed using a Markov model reflecting likely care pathways. RESULTS: 156 reports describing 88 RCTs were included. Most had fewer than 100 participants (range 12-234). TURP provided consistent, high-level, long-term symptomatic improvement. Minimally invasive procedures resulted in less marked improvement. Ablative procedures gave improvements equivalent to TURP. Holmium laser enucleation of the prostate (HoLEP) additionally resulted in greater improvement in flow rate. HoLEP is unique amongst the newer technologies in offering an advantage in urodynamic outcomes over TURP, although long-term follow-up data are lacking. Severe blood loss was more common following TURP. Rates of incontinence were similar across all interventions other than transurethral needle ablation (TUNA) and laser coagulation, for which lower rates were reported. Acute retention and reoperation were commoner with newer technologies, especially minimally invasive interventions. The economic model suggested that minimally invasive procedures were unlikely to be cost-effective compared with TURP. Transurethral vaporisation of the prostate (TUVP) was both less costly and less effective than TURP. HoLEP was estimated to be more cost-effective than a single TURP but less effective than a strategy involving repeat TURP if necessary. The base-case analysis suggested an 80% chance that TUVP, followed by HoLEP if required, would be cost-effective at a threshold of 20,000 pounds per quality-adjusted life-year. At a 50,000 pounds threshold, TUVP, followed by TURP as required, would be cost-effective, although considerable uncertainty surrounds this finding. The main limitations are the quantity and quality of the data available, in the context of multiple comparisons. CONCLUSIONS: In the absence of strong evidence in favour of newer methods, the standard--TURP--remains both clinically effective and cost-effective. There is a need for further research to establish (i) how many years of medical treatment are necessary to offset the cost of treatment with a minimally invasive or ablative intervention; (ii) more cost-effective alternatives to TURP; and (iii) strategies to improve outcomes after TURP.


Assuntos
Hipertermia Induzida , Terapia a Laser , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata , Resultado do Tratamento , Idoso , Análise Custo-Benefício , Bases de Dados Bibliográficas , Humanos , Hipertermia Induzida/economia , Hipertermia Induzida/métodos , Terapia a Laser/economia , Lasers de Estado Sólido/uso terapêutico , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/economia , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/fisiopatologia , Avaliação da Tecnologia Biomédica/economia , Ressecção Transuretral da Próstata/economia , Ultrassonografia
5.
Health Serv Manage Res ; 18(4): 265-76, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16259674

RESUMO

OBJECTIVE: To review and critically evaluate a multidisciplinary independent evaluation of business process re-engineering within a UK hospital using routine data. METHODS: Routine data measures of hospital cost efficiency are used to compare rates of changes at Leicester Royal Infirmary (LRI) with a 'peer group' of 22 teaching hospitals and to ascertain changes attributable to re-engineering. Different adjustment factors are quantified and the robustness of individual measures discussed. In addition to providing context to the quantitative primary research and the qualitative research on change management, service performance and quality indicators not captured in overall efficiency measures are assessed using detailed routine data measures. RESULTS: LRI is one of the most efficient teaching hospitals in England and continued improvement during re-engineering is shown to be at a faster rate than the peer group average, although attribution of changes is difficult. Lack of availability and inconsistency of data for support services meant that many re-engineering initiatives are not quantifiable using routine data measures. CONCLUSIONS: When combining different measures, routine data is a valuable tool in evaluating organizational change initiatives. However, use in future evaluations would require consistent benchmarking of routine data.


Assuntos
Análise Custo-Benefício , Estudos de Avaliação como Assunto , Hospitais de Ensino/organização & administração , Inovação Organizacional , Benchmarking , Hospitais de Ensino/economia , Qualidade da Assistência à Saúde , Medicina Estatal , Reino Unido
8.
Pharmacoeconomics ; 17(2): 151-65, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10947338

RESUMO

Given the growing need to value health-related quality of life, a review of the literature relating to health state valuation techniques was undertaken to appraise the current theoretical and empirical evidence available to inform on the techniques, to identify consensus, identify disagreement and identify important areas for future research. A systematic search of the literature was conducted, covering standard gamble (SG), time trade-off (TTO), visual analogue scale (VAS), magnitude estimation (ME) and person trade-off (PTO) techniques. The basic concepts of practicality, reliability, theoretical validity and empirical validity formed the criteria for reviewing the performance of valuation techniques. In terms of practicality and reliability, we found little evidence relating to ME and PTO. SG, TTO and VAS have been shown to be practical on a range of populations. There is little difference between the reliability of SG, TTO and VAS, and present evidence does not offer a basis to differentiate between them. When considering the theoretical basis of techniques, we conclude that choice-based methods (i.e. SG, TTO and PTO) are best placed to reflect the strength of preference for health, with the choice between these techniques depending on the study characteristics and the perspective employed. Empirical evidence relating to the theoretical perspective of the techniques has shown that there are problems with all techniques in terms of descriptive validity.


Assuntos
Qualidade de Vida , Economia , Humanos , Qualidade de Vida/psicologia
9.
Neuropharmacology ; 38(12): 1811-7, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10608276

RESUMO

The pharmacological properties of [3H]ATPA ((RS)-2-amino-3(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid) are described. ATPA is a tert-butyl analogue of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid) that has been shown to possess high affinity for the GluR5 subunit of kainate receptors. [3H]ATPA exhibits saturable, high affinity binding to membranes expressing human GluR5 (GluR5) kainate receptors (Kd approximately 13 nM). No specific binding was observed in membranes expressing GluR2 and GluR6 receptors. Several compounds known to interact with the GluR5 kainate receptor inhibited [3H]ATPA binding with potencies similar to those obtained for competition of [3H]kainate binding to GluR5. Saturable, high affinity [3H]ATPA binding (Kd approximately 4 nM) was also observed in DRG neuron (DRG) membranes isolated from neonatal rats. The rank order potency of compounds to inhibit [3H]ATPA binding in rat DRG and GluR5 membranes were in agreement. These finding demonstrate that [3H]ATPA can be used as a radioligand to examine the pharmacological properties of GluR5 containing kainate receptors.


Assuntos
Agonistas de Aminoácidos Excitatórios/farmacocinética , Gânglios Espinais/metabolismo , Isoxazóis/farmacocinética , Ácido Caínico/metabolismo , Neurônios/metabolismo , Propionatos/farmacocinética , Receptores de Ácido Caínico/metabolismo , Animais , Animais Recém-Nascidos , Linhagem Celular , Humanos , Ratos , Receptores de Ácido Caínico/genética
11.
J Health Serv Res Policy ; 4(3): 174-84, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10538884

RESUMO

OBJECTIVE: To review the use of measures of health status in the assessment of benefits in economic evaluation, whether or not the measures were designed for this purpose. METHODS: The review was based on a systematic search of the literature. It provides a comprehensive assessment of the evidence where it exists and a balanced overview of opinion otherwise. RESULTS: Over 3000 papers were identified, of which 632 were found to be relevant. The review provides a set of recommendations. These include: a checklist of questions for selecting a measure for use in economic evaluation; a list of circumstances in which non-preference-based measures can be used; and recommendations surrounding the use of health state valuation techniques and multi-attribute utility scales. CONCLUSION: These recommendations should help to identify poor economic evaluations and hence guard against inefficient conclusions being drawn regarding the provision of health services.


Assuntos
Pesquisa sobre Serviços de Saúde/economia , Indicadores Básicos de Saúde , Análise Custo-Benefício , Alocação de Recursos para a Atenção à Saúde , Pesquisa sobre Serviços de Saúde/métodos , Inquéritos Epidemiológicos , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Projetos de Pesquisa , Reino Unido/epidemiologia
13.
Health Econ ; 8(1): 41-51, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10082142

RESUMO

There have been a number of published reviews of measures of health related quality of life, but most of this work has been undertaken within a tradition of psychometrics outside of economics. This situation has often resulted in health status measures designed specifically for the purposes of economic evaluation being neglected and portrayed as 'invalid'. This paper utilizes and adapts the traditional psychometric concepts of practicality, reliability and validity for judging preference-based measures of health related quality of life. The psychometric and economic approaches are most different in relation to validity because they are seeking to measure different concepts. The former seeks to measure health change as perceived by patients, whilst economic evaluation requires a measure of the value or strength of preference for the health change. A checklist is presented to provide guidance in the design or review of economic evaluations using changes in health as the main measure of benefit.


Assuntos
Pesquisa sobre Serviços de Saúde/economia , Psicometria/métodos , Anos de Vida Ajustados por Qualidade de Vida , Guias como Assunto , Pesquisa sobre Serviços de Saúde/métodos , Humanos , Reprodutibilidade dos Testes
14.
J Adv Nurs ; 29(1): 44-51, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10064281

RESUMO

Tameside and Glossop rehabilitation team (in England) have developed a progressive and targeted service for people with serious mental health problems through the systematic implementation of research-based evidence in practice and service configuration. This study was undertaken to provide a method of auditing the clinical outcome of the service and monitoring staff morale in a manner which could be integrated in the day to day delivery of services, and which could inform future service developments. Changes in the functioning of the total population of rehabilitation team clients were assessed over a 1-year period by Health of the Nation Outcome Scales (HoNOS) ratings at 6-monthly intervals. Factors causing stress and stress levels among all staff were assessed using the Mental Health Stress Questionnaire. The findings give clear indications of areas of the service which needed improving or changing, and identify ways in which the ongoing process of data collection might be refined.


Assuntos
Serviços Comunitários de Saúde Mental/organização & administração , Transtornos Mentais/reabilitação , Moral , Avaliação de Resultados em Cuidados de Saúde/métodos , Equipe de Assistência ao Paciente , Benchmarking/métodos , Serviços Comunitários de Saúde Mental/métodos , Coleta de Dados/métodos , Inglaterra , Humanos , Transtornos Mentais/economia , Transtornos Mentais/enfermagem , Recursos Humanos de Enfermagem/psicologia , Estresse Psicológico/psicologia
15.
Neuropharmacology ; 37(10-11): 1261-7, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9849663

RESUMO

The activity of a gamma-substituted glutamate analogue, (2S, 4R, 6E)-2-amino-4-carboxy-7-(2-naphthyl)hept-6-enoic acid (LY339434) and (2S,4R)-4-methylglutamic acid at ionotropic glutamate receptors has been examined. Ligand binding studies were performed using [3H] AMPA binding to membranes expressing either homomeric recombinant GluR1, GluR2, GluR4 receptors, and [3H] kainate binding to GluR5 and GluR6 kainate receptors. LY339434 and (2S,4R)-4-methylglutamic acid showed selectivity in ligand binding studies for kainate receptors over AMPA receptors. Within the kainate class of glutamate receptors, LY339434 showed selectivity for GluR5 over GluR6 whereas (2S,4R)-4-methylglutamic acid showed high affinity for both GluR5 and GluR6 kainate receptors. Examination of the functional activity of LY339434 and (2S,4R)-4-methylglutamic acid showed that both compounds evoked inward currents in dorsal root ganglion neurons (DRG) with estimated EC50 values of 0.8 +/- 0.2 microM and 0.17 +/- 0.04 microM, respectively. In GluR5 expressing HEK 293 cells, LY339434 evoked inward currents with an estimated EC50 value of 2.5 +/- 0.9 microM but had little effect on GluR6 expressing cells at concentrations less than 100 microM. LY339434 was a weak AMPA receptor agonist (EC50 values > 300 microM) as determined by activity in acutely isolated cerebellar Purkinje neurons. LY339434 and (2S,4R)-4-methylglutamic acid had agonist activity at NMDA receptors studied in cultured hippocampal neurons with EC50s of 2.5 microM and 11.7 microM, respectively. These results indicate that both LY339434 and (2S,4R)-4-methyl glutamic acid may be useful pharmacological tools for the examination of kainate receptors.


Assuntos
Aminoácidos/farmacologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Glutamatos/farmacologia , Glutaratos/farmacologia , Hipocampo/efeitos dos fármacos , Receptores de AMPA/efeitos dos fármacos , Receptores de Ácido Caínico/efeitos dos fármacos , Aminoácidos/metabolismo , Animais , Células Cultivadas , Glutaratos/metabolismo , Hipocampo/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Receptores de Ácido Caínico/metabolismo
16.
Neuropharmacology ; 37(1): 25-36, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9680256

RESUMO

In order to study the roles of the AMPA and kainate subtypes of non-NMDA glutamate receptors in the processing of persistent nociceptive information, compounds with varying activities at these receptors were examined for effects on the formalin-induced paw-licking behavior in rats. The selective AMPA antagonist, LY300164 and the mixed AMPA/kainate antagonist, NBQX, were compared for their effects on formalin-induced pain behavior. NBQX (3, 10, 20 mg/kg, i.p.), caused antinociception as well as ataxia whereas the selective AMPA antagonist, LY300164 (3,5,10 mg/kg, i.p.), did not cause antinociception at doses that did not produce ataxia. In view of the well documented distribution of kainate receptors on C fibres and of the kainate-preferring iGluR5 subtype on dorsal root ganglia (DRG), we tested a series of three decahydroisoquinolines with different profiles of activity between iGluR5 and AMPA receptors and all without activity on iGluR6, iGluR7 or KA2 subtypes. LY293558 (0.1, 1, 3, 5 mg/kg, i.p.), which had low micromolar affinity for both iGluR5 and 2 caused, like NBQX, both antinociceptive and ataxic effects. However, the selective iGluR5 antagonist LY382884 (5, 10, 30, 100 mg/kg, i.p.), exhibited antinociceptive actions without ataxia while the iGluR2 preferring antagonist LY302679 (5 mg/kg, i.p), caused ataxia but did not produce antinociceptive effects at that dose. These actions were stereoselective since the enantiomeric compounds, LY293559 and LY302680, were ineffective in these tests. The data strongly suggest an involvement of iGluR5 in the processing of nociceptive information.


Assuntos
Antagonistas de Aminoácidos Excitatórios/farmacologia , Limiar da Dor/fisiologia , Receptores de Ácido Caínico/fisiologia , Animais , Benzodiazepinas/metabolismo , Benzodiazepinas/farmacologia , Antagonistas de Aminoácidos Excitatórios/metabolismo , Formaldeído , Humanos , Isoquinolinas/metabolismo , Isoquinolinas/farmacologia , Masculino , Quinoxalinas/metabolismo , Quinoxalinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Ácido Caínico/efeitos dos fármacos , Tetrazóis/metabolismo , Tetrazóis/farmacologia
17.
Pharmacoeconomics ; 13(4): 411-20, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10178665

RESUMO

There are now a large number of instruments available for assessing health-related quality of life, many of which are used within economic evaluations. When considering the use of quality-of-life instruments, meaningful questions need to be asked to determine whether an instrument has been used judiciously. Such questions should consider whether the instrument is valid and suitable for the particular study question, whether the instrument is compatible with the economic evaluation framework used, and subsequently whether the conclusions presented in the study are legitimate. In order to illustrate the value of these questions we have applied them to a number of economic evaluations. The studies used were identified via a systematic review of the health economics literature. In our assessment of a sample of published material, we found that reporting is frequently unhelpful and that the inappropriate use of instruments and techniques casts doubt on the conclusions of economic evaluations. Furthermore, our systematic review of the health economics literature has shown that the general format of reported economic evaluations falls short of the commonly accepted ideal. We examined the health economics literature for 1995 and only identified a handful of studies which satisfied the economic evaluation criteria as accepted by most economists. It is hoped that raising awareness of these issues will urge evaluators, referees and publishers not to lose sight of the needs of the decision-maker when considering the detail which should be present in a reported evaluation.


Assuntos
Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Economia , Humanos
18.
J Med Chem ; 40(22): 3645-50, 1997 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-9357531

RESUMO

Both willardiine and azawillardiine analogs (18-28) have been reported to be potent and selective agonists for either AMPA or kainate receptors. We report here the novel synthesis and pharmacological characterization of a range of willardiine (18-23) and 6-azawillardiine (24-28) analogs on cells individually expressing human homomeric hGluR1, hGluR2, hGluR4, or hGluR5 receptors. Reaction of the sodium salts of substituted uracils (7-12) or 6-azauracils (13-16) with (S)-3-[(tert-butoxycarbonyl)amino]oxetan-2-one (17) in dry DMF, subsequent deprotection in TFA, and purification by ion-exchange chromatography gave mainly the willardiine analog in which alkylation took place on N1 of the uracil ring. We have investigated the subtype selectivity of these compounds by examining their binding affinity for homomeric hGluR1, -2, -4, or -5 (and hGluR6 in the case of 5-iodowillardiine (22)). From this study we have demonstrated that 22 has high affinity for hGluR5 and, compared to kainate, displays excellent selectivity for this receptor over both the AMPA receptor subtypes and the homomeric kainate receptor, hGluR6. 5-Fluorowillardiine (19) has higher affinity than AMPA for both homomeric hGluR1 and hGluR2 and compared to AMPA displays greater selectivity for AMPA receptor subtypes over the kainate receptor, hGluR5. Some structural features required for optimal activity at homomeric AMPA or kainate receptor subtypes have also been identified. It would appear that quite large lipophilic substituents at the 5-position of the uracil ring not only are accommodated by hGluR5 receptors but also lead to enhanced affinity for these receptors. In contrast to this, for optimal binding affinity to hGluR1, -2, or -4, smaller, electron-withdrawing substituents are required. For optimal activity at hGluR4 receptors a 6-aza-substituted willardiine is favored. The subtype-selective compounds described here are likely to be useful tools to probe the distribution and the physiological roles of the various glutamate receptor subunits in the central nervous system.


Assuntos
Alanina/análogos & derivados , Agonistas de Aminoácidos Excitatórios/síntese química , Receptores de AMPA/agonistas , Receptores de Ácido Caínico/agonistas , Triazinas/síntese química , Alanina/síntese química , Alanina/metabolismo , Alanina/farmacologia , Linhagem Celular , Agonistas de Aminoácidos Excitatórios/metabolismo , Agonistas de Aminoácidos Excitatórios/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Pirimidinonas , Ensaio Radioligante , Receptores de AMPA/genética , Receptores de AMPA/metabolismo , Receptores de Ácido Caínico/genética , Receptores de Ácido Caínico/metabolismo , Proteínas Recombinantes/agonistas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Triazinas/farmacologia , Uracila
19.
Br J Gen Pract ; 47(424): 699-703, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9519514

RESUMO

BACKGROUND: Nurses trained in ear care provide a new model for the provision of services in general practice, with the aim of cost-effective treatment of minor ear and hearing problems that affect well-being and quality of life. AIM: To compare a prospective observational cohort study measuring health outcomes and resource use for patients with ear or hearing problems treated by nurses trained in ear care with similar patients treated by standard practice. METHOD: A total of 438 Rotherham and 196 Barnsley patients aged 16 years or over received two self-completion questionnaires: questionnaire 1 (Q1) on the day of consultation and questionnaire 2 (Q2) after three weeks. Primary measured outcomes were changes in discomfort and pain; secondary outcomes included the effect on normal life, health status, patient satisfaction, and resources used. RESULTS: After adjusting for differences at Q1, by Q2 there was no statistical evidence of a difference in discomfort and pain reduction, or differential change in health status between areas. Satisfaction with treatment was significantly higher (P = 0.0001) in Rotherham (91%) than in Barnsley (82%). Average total general practitioner (GP) consultations were lower in Rotherham at 0.4 per patient with an average cost of 6.28 Pounds compared with Barnsley at 1.4 per patient and an average cost of 22.53 Pounds (P = 0.04). Barnsley GPs prescribed more drugs per case (6% of total costs compared with 1.5%) and used more systemic antibiotics (P = 0.001). CONCLUSIONS: Nurses trained in ear care reduce costs, GP workload, and the use of systemic antibiotics, while increasing patient satisfaction with care. With understanding and support from GPs, such nurses are an example of how expanded nursing roles bring benefits to general practice. Nurses trained in ear care reduce treatment costs, reduce the use of antibiotics, educate patients in ear care, increase patient satisfaction, and raise ear awareness.


Assuntos
Otopatias/enfermagem , Profissionais de Enfermagem , Atenção Primária à Saúde/organização & administração , Adulto , Idoso , Estudos de Coortes , Análise Custo-Benefício , Inglaterra , Feminino , Transtornos da Audição/enfermagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida
20.
Qual Health Care ; 5(4): 193-200, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10164142

RESUMO

OBJECTIVE: To document the nature of audit activity at the primary-secondary care interface; to explore participants' experiences of undertaking such interface audit; to identify factors associated with these experiences; and to gather views on future interface audit activities. DESIGN: A three phase national survey by postal questionnaire with a cascade sampling approach. SETTING: England and Wales. RESULTS: Response rates were: 65% to the first questionnaire; 34% to the second questionnaire; and 45% to the third questionnaire. 56% of the audits covered some element of management of patients or disease; only 33% of the audits were within a single topic area. Most audits had more than one trigger: for 61% the trigger was a perceived problem; for 58% it was of mutual interest. Only 18% of audits were initiated collaboratively; doctors were the most frequent initiators (72%), and most audits (63%) involved collaborative groups convened specifically for the audit. 58% of groups had between three and eight members, 23% had 12 or more. Doctors were the most frequent group members. There was differential involvement of group members in various group tasks; the setting of guidelines was highly dominated by doctors. Of reportedly complete audits, only two fifths had implemented change and only a quarter had evaluated this change. There was widespread feeling of successful group work, with evidence of benefit in terms of the two sectors of care being able to consider issues of mutual concern. Levels of understanding of the group task and of participation were positively related to the duration of meetings. Joint initiation of audits facilitated greater understanding of the group task. Larger group sizes allowed primary and secondary carers to discuss issues of common concern; however, larger groups were more likely to experience disagreements. Having previously worked with group members increased trust and good working relations. The main lessons learnt from the experience included the importance of setting clear objectives and good communications between primary and secondary carers. Factors identified as important for future audit activity at the primary-secondary care interface included commitment, enthusiasm, time, and money. CONCLUSIONS: Audit at the primary-secondary care interface is taking place on a wide scale and has been an enjoyable experience for most of the respondents in this study. IMPLICATIONS: Despite being a positive experience most audits stopped short of implementing change. Care must be taken to complete the audit cycle if audit at the primary-secondary care interface is to move beyond the roles of education and professional development and to fulfil its potential in improving the quality of care.


Assuntos
Pesquisas sobre Atenção à Saúde/métodos , Auditoria Médica/estatística & dados numéricos , Atenção Primária à Saúde/normas , Encaminhamento e Consulta/normas , Inglaterra , Medicina Estatal/normas , Inquéritos e Questionários , País de Gales
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